Emily Porter
Pronouns: She/her
Research Mentor(s): Sethuramasundaram Pitchiaya
Research Mentor School/College/Department: Urology / Medicine
Program: UROPF
Session: Session 6 (3:40pm – 4:30pm)
Authors: Emily Porter, Joel Berends, Sethu Pitchiaya
Abstract
When exposed to environmental stress, mammalian cells invoke evolutionarily conserved measures that help restore protein and cellular homeostasis. These responses include the induction of chaperone genes by transcription factors like heat shock factors (HSFs), which together aid appropriate protein folding and mitigate the formation of toxic protein aggregates. The aberration of this proteostasis mechanism is a hallmark of ageing and several neurodegenerative pathologies. We find that HSF1 accumulates within nuclear membraneless organelles, termed nuclear stress bodies (nSBs), in response to a variety of stresses to possibly induce proteostatic transcriptional activity. Here, we sought to determine the protein composition of nSBs, which helps to delineate nSB function. We posited that proteins that interacted with HSF1 were likely to co-accumulate with HSF1 in nSBs; therefore so we selected protein candidates from the literature, based on studies that curated HSF1 interactome by immunoprecipitation and mass spectrometry respectively. We modeled heat stress in human U2-OS (osteosarcoma) cell line. Immunolabeling followed by super-resolution fluorescence microscopy was used to visualize HSF1 and other proteins and image analysis was performed to assess whether HSF1 interactors colocalized with HSF1 in nSBs. We find that some HSF1 interactors, such as HSF2 accumulate within nSBs whereas others, such as HSP90, do not. Knowing which proteins co-localize with HSF1 in nSBs and whether this aspect changes with different stresses will reveal the context-specific function of these membraneless organelles in both physiology and pathology.
